We propose a Center for Health Systems Research at an integrated safety net health system, predicated on the view that the safety net can provide lessons about efficiency that the entire healthcare system can learn from. The Center's theme will be system design for the disadvantaged in the context of the resource constraints that are unique to the safety net, thus emphasizing both reduction of health disparities in the underserved and comparison of delivery system designs. We will partner with an academic research unit and an applied healthcare research organization to develop a research infrastructure and to create collaborations that will sustain meaningful patient-centered outcomes research well into the future. Infrastructure development includes building the methodological skills of our emerging investigators through a highly structured teaching and mentorship program, and development of a cross-institution data integration structure that will begin to connect us with much larger research networks. We will demonstrate functionality of the data integration structure with a description of the geography of depression in Denver. We will assess the effectiveness of novel interventions for weight management, for asthma care in high risk patients, and for dual contraception and STD/HIV prevention in three related projects.